This proposal involves an interdisciplinary approach to characterize and localize in nervous tissue, immunologic and viral factors implicated in the demyelinating diseases, particularly multiple sclerosis (MS). Immunoglobulins will be purified from the blood, cerebrospinal fluid (CSF) and eluted from central nervous system (CNS) tissue of afflicted subjects and controls and tested immunocytochemically upon sections and organotypic cultures of CNS tissue. Attempts will be made to determine the nature of the target antigens in this group of diseases. One antigen under survey is the oligodendrocyte and this will be followed in MS plaques of different ages using ultrastructure and immunocytochemistry on preparations treated with a highly specific, well-characterized antioligodendrocyte serum raised in rabbits in these laboratories. Parallel studies will be carried out using similar samples from guinea pigs with chronic, relapsing experimental allergic encephalomyelitis (EAE), a model which mimics, in many regards, the course and pathology of MS. From these animals, longitudinally sampled serum, lymphocyte populations and IgG eluted from the CNS will be tested on CNS cultures for fluctuations in their ability to cause demyelination. A separate, but related, group of experiments on guinea pigs will involve the search for myelin lipids which, when combined with myelin basic protein, produce full blown demyelinating disease in animals and myelinotoxic serum factors as tested in vitro. Viral antigens, in particular measles and herpes, will be sought in tissues from MS and Landry Guillain Barre Syndrome by ultrastructural and immunocytochemical techniques. The experiments on the possible involvement of paramyxovirus antigens in MS will be complemented by virologic studies on cell-associated and cell-free strains of SSPE virus grown in cell lines and nervous tissue.